The New Gladiators Flashcards
The medical term for “punched drunk”
dementia pugilisitca
What part of the brain is implicated in the dementia pugilisitca study of boxers’ brains
Anterior temporal cortex
The cell density was much decreased
Fusiform Gyrus of the temporal lobe had tau
Pathological hallmark of many neuropathies
tau
In other words, Neurofibrillary Tangles
The Neurological Effects of Boxing
Neurofibrillary tangles (tau) in the Substantia Nigra and Cerebral Cortex
Few senile plaques (β-amyloid), so the damage wasn’t just the effect of the boxers aging.
Fusiform gyrus
– Recognition functions
• Word
• People
Depigmentation of the Substantia Nigra, which is responsible for dopamine production.
Parkinson’s
Cerebellar Tonsils were consistently damaged
Gliosis
Pattern of Purkinje Cell Loss
What is the Fusiform Gyrus known for?
Recognition functions:
• Words
• People
senile plaques
(β-amyloid)
Senile plaques (aka, neuritic plaques, senile druse, braindruse) are Extracellular Deposits of Amyloid Beta in the Grey matter of the brain.
Degenerative neural structures and an abundance of microglia & astrocytes can be associated with senile plaque deposits.
These deposits can also be a byproduct of senescence (ageing).
However, large numbers of senile plaques and neurofibrillary tangles are characteristic features of Alzheimer’s disease.
Abnormal neurites in senile plaques are composed primarily of paired helical filaments, a component of Neurofibrillary Tangles.
The plaques are variable in shape & size. In Alzheimer’s disease, they are primarily composed of amyloid beta peptides.
These polypeptides tend to Aggregate and are believed to be Neurotoxic.
What is the Substantia Nigra known for?
dopamine production
The substantia nigra is critical in the development of Parkinson’s disease.
Parkinson’s disease is a neurodegenerative disease characterized, in part, by the death of dopaminergic neurons in the pars compacta of the substantia nigra.
The major symptoms of Parkinson’s disease include tremor, akinesia, bradykinesia, and stiffness. Other symptoms include disturbances to posture, fatigue, sleep abnormalities, and depressed mood.
The cause of death of dopaminergic neurons in the pars compacta is unknown. However, some contributions to the unique susceptibility of dopaminergic neurons in the pars compacta have been identified.
For one, dopaminergic neurons show abnormalities in mitochondrial complex 1, causing aggregation of alpha-synuclein; this can result in abnormal protein handling and neuron death.
Secondly, dopaminergic neurons in the pars compacta contain less calbindin than other dopaminergic neurons.
Calbindin is a protein involved in calcium ion transport within cells, and excess calcium in cells is toxic. The calbindin theory would explain the high cytotoxicity of Parkinson’s in the substantia nigra compared to the ventral tegmental area.
Regardless of the cause of neuronal death, the plasticity of the pars compacta is very robust; Parkinsonian symptoms do not appear until up to 50-80% of pars compacta dopaminergic neurons have died.
Most of this plasticity occurs at the neurochemical level; dopamine transport systems are slowed, allowing dopamine to linger for longer periods of time in the chemical synapses in the striatum.
The Generation of Septum Cavum
Septum Pellucidum— Corpus callosum to fornix
• SP separates creating cavum
• Detaches from corpus callosum
• And/or fenestrated
Part of limbic system – Reward – Memory – Emotion 
Septum pellucidum is the name of the normal structure. It is a ribbon-like structure made of axonal projections from the corpus callosum to the fornix that contributes to the separation of the lateral ventricles.
With repeated head trauma (i.e. boxing), the pellucidum can separate and/or become fenestrated. The separation forms a new space or “cavum” that otherwise isn’t normally there.
Note the table on slide 10 with most of the controls not having a cavum.
fenestration = a perforation in a structure.
Boxers Have Cava and Fenestrations in Septum
Percentage of boxers WITHOUT cavum or fenestration: 0%
Percentage of boxers with either a cavum OR fenestration: 100%
Percentage of boxers with both cavum AND fenestration: 77%
~~~~~~~~~~
Percentage of NON-boxers WITHOUT cavum OR fenestration: 66%
Percentage of NON-boxers with cavum AND fenestration: 3%
Cerebellar Tonsils
The cerebellar tonsil is analogous to a rounded lobule on the undersurface of each cerebellar hemisphere.
Synonym: tonsilla cerebelli.
The flocculonodular lobe of the cerebellum is one of 3 lobes that make up the overall composition of the cerebellum.
The cerebellum consists of 3 anatomical and functional lobes: anterior lobe, posterior lobe, and flocculonodular lobe.
Elongation of the cerebellar tonsils can, due to Pressure, lead to this portion of the cerebellum to slip or be pushed through the Foramen Magnum of the skull resulting is tonsillar herniation.
This is a life-threatening condition as it causes increased pressure on the medulla oblongata which contains respiratory and cardiac control centres.
Gliosis in Molecular Layer
Gliosis in Molecular Layer • GFAP in Red • Purkinje in Green • Dapi 
Gliosis
Gliosis is a nonspecific reactive change of glial cells in response to damage to the CNS.
In most cases, gliosis involves the proliferation or hypertrophy of several different types of glial cells, including astrocytes, microglia, and oligodendrocytes.
Indicative of a shift to an inflammatory state
Indication of cell death in boxers
Pattern of Purkinje Cell Loss, specifically in the cerebellum
Pathological Summary of the Boxer’s Study
- abnormalities of the septum pellucidum (cavum, fenestrations);
- cerebellar scarring on the inferior surface of the lateral lobes, most marked in the tonsillar region and loss of Purkinje cells in these areas
- degeneration of the substantia nigra with loss of pigmentation, neurofibrillary changes, and no Lewy bodies.
- widespread neurofibrillary tangles in the cerebral cortex and brainstem, most prominently in the medial temporal lobe gray matter; sparsity, or in most cases, the total absence of senile plaques.
Lewy bodies
Lewy bodies are abnormal aggregates of protein that develop inside nerve cells in Parkinson’s disease (PD), Lewy body dementia, and some other disorders.
They are identified under the microscope when histology is performed on the brain.
Football Players Replace Boxers as Gladiators
Boxing waning in popularity
NFL = $9Billion in annual revenues
In 2010, the collective revenue of the 15
highest-grossing football programs in the
U.S. was more than $1 billion (http://finance.zacks.com/much-money-college-sports-generate-10346.html)
Mike Webster
1952–2002
• Center
• 4x Champion, 9x Pro Bowler
• NFL 75th Anniversary All-Time Team
• Played from 1974-1990
• Every offensive snap for 10 consecutive years
• He earned $16,000 in his first season, $400,000 in his last.
• 6’1” 255lbs
• Maurkice Pouncey: 6’4” 304lbs
• Post Retirement: amnesia, dementia, depression
• Lived in pickup truck/train stations
–Declined help from friends
• Moved in with teenage son
• Mood swings, inconsistent train of thought, indecisive
• Died 50 yo
Mike Webster Autopsy
• Originally reported as coronary related event
– Since retracted
• Brain analyzed by Bennet Omalu in 2002
• Results published in Neurosurgery 2005
• 18 reviewers (a ton of reviewers)
• no cortical atrophy, cortical contusion, hemorrhage, or infarcts
• Mild neuronal dropout—frontal, parietal and temporal neocortex
• Diffuse amyloid plaques, neurofibrillary tangles, Tau+ threads in neocortex
• “potential long-term neurodegenerative outcomes in retired professional National Football League players subjected to repeated mild traumatic brain injury.”
Webster Disability Claim
• 1999—Webster filed for permanent disability benefits • Originally denied then reversed • Admitted football caused brain injuries • Argued injuries started after career • Offered lower payments • NFL ultimately lost on appeal in 2006 (7-yr battle) • $2M to Webster family
NFL—CTE Denier
Judge approved $900Billion settlement to concussion lawsuits
• Publicly denied link between football and brain injury
• Settled disability lawsuits—including Mike Webster
• Book/Movie–“League of Denial”
• Class action lawsuit–$900M settlement
– 4,500 former players (or their estates) participated
– 25,000 retired players eligible
– 65years
League of Denial
• Book • Frontline: http://www.pbs.org/wgbh /pages/frontline/league- of-denial/  Will Smith
Modern Athletes = New Gladiators
- Risk life for entertainment
- Football–Dave Duerson, Mike Webster, Andre Waters, Jovan Belcher, Chris Henry, Junior Seau
- Wrestlers— Chris Benoit
- Soccer–Bellini—1958 Brazilian World Cup Captain
Clinical Presentation of Chronic Traumatic Encephalopathy (CTE)
• Retrospective study of 36 cases from Boston University Center for the Study of Traumatic Encephalopathy brain bank
• Athletes: – Football =29 (3 through college, 3 through HS) – Hockey = 3 – Professional Wrestling = 1 – Boxers = 3 (1 pro, 2 amateur)
• No comorbid neurodegenerative disease
Could only study CTE post-humously, which is a setback
Initial Presentation of CTE
Very Heterogenous
• 31%–Cognitive Deficits
– Episodic memory impairment
– Executive dysfunction
• 36%–Behavioral Changes
– Explosivity
– Impulsivity
– Violence
• 25%–Mood Changes
– Depression
– Hopelessness
• 8%–Asymptomatic
Group Demographics:
• Behavior and Mood were
combined
• E4/E4 allele largest known risk factor for Alzheimer’s –> only 18%
CTE Symptoms Throughout Life
Broken out by initial onset
These groups did not have the symptoms of dementia (like apathy and disinhibited speech), these symptoms set CTE apart
CTE Clinical Summary
• 2 Presentations:
Behavior/Mood and Cognitive
– Behavior/Mood onset is younger (34 vs 58 yo)
- B/M group almost always progressed to cognitive impairment
- Control group rarely showed B/M issues
- Control group more likely to progress to dementia (7 of 10 dementia diagnoses presented as Control)
- Low number for definite conclusions
- Motor features NOT prominent
CTE Distinguishing Features
Early presentation similar to frontotemporal dementia (FTD)
– FTD patients exhibit disinhibited/inappropriate
behavior/speech, apathy
– CTE disinhibition and apathy were infrequent in CTE cases
Progressive memory loss resembles Alzheimer’s though pathologically distinct
Caveats
• Small study (generalizability of results??) • Selection bias • Reliability of retrospective reports • No athlete controls
The brains that are most likely to end up at the bank are from situations of relational turmoil, not people who had the disease but were asymptomatic or brains of people who had many symptoms but were socially isolated. It studies after the subjects are dead, so you’re super dependent on the loved-ones’ selective memories and representations of things, who forget details or maybe are slow to become aware of certain symptoms. Psychologists and medical docs were not there to diagnose issues that the average person may not identify
CTE and NFL Brains
neurofibrillary tangles = NFT
Boston University CTE Center
59 of 62 NFL player brains positive for CTE
Update: 87 out of 91 players test positive for CTE
CTE Recognition In Many Athletes
Soccer, Hockey, Rugby • Soldiers (blast injuries) • Abuse • Autism • Epilepsy 
Current Grading of CTE
- Four grades
- Post mortem
- Regions/abundance
